Methods of and pharmaceutical compositions for improving implantation of embryos

Abstract

Methods of improving embryo implantation are disclosed and comprise contacting a receptive uterus and/or an embryo with an effective amount of heparanase and implanting the embryo in the receptive uterus.

1 . A method of improving embryo implantation, the method comprising contacting an embryo with an effective amount of purified heparanase, said heparanase having or being activatable to have catalytic activity as an active form of a heparanase protein as set forth by SEQ ID NO:5, so as to improve embryo implantation, and implanting the embryo in a receptive uterus.  
     
     
         2 . The method of  claim 1 , wherein said heparanase is a mature heparanase.  
     
     
         3 . The method of  claim 1  wherein said heparanase is a pro-heparanase, cleavable into mature heparanase.  
     
     
         4 . The method of  claim 1 , wherein contacting the embryo with an effective amount of heparanase is in vitro.  
     
     
         5 . The method of  claim 1 , wherein contacting the embryo with an effective amount of heparanase is in utero.  
     
     
         6 . The method of  claim 1 , wherein the embryo is generated in vitro via in vitro fertilization.  
     
     
         7 . A method of improving embryo implantation, the method comprising contacting a receptive uterus with an effective amount of purified heparanase, said heparanase having or being activatable to have catalytic activity as an active form of a heparanase protein as set forth by SEQ ID NO:5, so as to improve embryo implantation and implanting the embryo in a receptive uterus.  
     
     
         8 . The method of  claim 7 , wherein said heparanase is a mature heparanase.  
     
     
         9 . The method of  claim 7 , wherein said heparanase is a pro-heparanase, cleavable into mature heparanase.  
     
     
         10 . The method of  claim 7 , wherein the embryo is generated in vitro via in vitro fertilization.  
     
     
         11 . The method of  claim 7 , wherein contacting the receptive uterus with the effective amount of heparanase precedes implanting the embryo in the receptive uterus.  
     
     
         12 . The method of  claim 7 , wherein contacting the receptive uterus with the effective amount of heparanase is concurrent to implanting the embryo in the receptive uterus.  
     
     
         13 . A method of improving embryo implantation, the method comprising contacting a receptive uterus with an effective amount of purified heparanase, said heparanase having or being activatable to have catalytic activity as an active form of a heparanase protein as set forth by SEQ ID NO:5, so as to improve embryo implantation, contacting an embryo with an effective amount of said heparanase and implanting the embryo in the receptive uterus.  
     
     
         14 . The method of  claim 13 , wherein said heparanase is a mature heparanase.  
     
     
         15 . The method of  claim 13 , wherein said heparanase is a pro-heparanase, cleavable into mature heparanase.  
     
     
         16 . The method of  claim 13 , wherein contacting the embryo with an effective amount of heparanase is in vitro.  
     
     
         17 . The method of  claim 13 , wherein contacting the embryo with an effective amount of heparanase is in utero.  
     
     
         18 . The method of  claim 13 , wherein the embryo is generated in vitro via in vitro fertilization.  
     
     
         19 . The method of  claim 13 , wherein contacting the receptive uterus with the effective amount of heparanase precedes implanting the embryo in the receptive uterus.  
     
     
         20 . The method of  claim 13 , wherein contacting the receptive uterus with the effective amount of heparanase is concurrent to implanting the embryo in the receptive uterus.  
     
     
         21 . A method of improving IVF embryo implantation, the method comprising contacting an IVF embryo with an effective amount of purified heparanase, said heparanase having or being activatable to have catalytic activity as an active form of a heparanase protein as set forth by SEQ ID NO:5, so as to improve embryo implantation, and implanting the embryo in a receptive uterus.  
     
     
         22 . The method of  claim 21 , wherein said heparanase is a mature heparanase.  
     
     
         23 . The method of  claim 21 , wherein said heparanase is a pro-heparanase, cleavable into mature heparanase.  
     
     
         24 . The method of  claim 21 , wherein contacting the IVF embryo with an effective amount of heparanase is in vitro.  
     
     
         25 . The method of  claim 21 , wherein contacting the IVF embryo with an effective amount of heparanase is in utero.  
     
     
         26 . A method of improving IVF embryo implantation, the method comprising contacting a receptive uterus with an effective amount of purified heparanase, said heparanase having or being activatable to have catalytic activity as an active form of a heparanase protein as set forth by SEQ ID NO:5, so as to improve embryo implantation, and implanting the IVF embryo in the receptive uterus.  
     
     
         27 . The method of  claim 26 , wherein said heparanase is a mature heparanase.  
     
     
         28 . The method of  claim 26 , wherein said heparanase is a pro-heparanase, cleavable into mature heparanase.  
     
     
         29 . The method of  claim 26 , wherein contacting the receptive uterus with the effective amount of heparanase precedes implanting the IVF, embryo in the receptive uterus.  
     
     
         30 . The method of  claim 26 , wherein contacting the receptive uterus with the effective amount of heparanase is concurrent to implanting the IVF embryo in the receptive uterus.  
     
     
         31 . A method of improving IVF embryo implantation, the method comprising contacting a receptive uterus with an effective amount of purified heparanase, said heparanase having or being activatable to have catalytic activity as an active form of a heparanase protein as set forth by SEQ ID NO:5, so as to improve embryo implantation, contacting an IVF embryo with an effective amount of said heparanase and implanting the IVF embryo in the receptive uterus.  
     
     
         32 . The method of  claim 31 , wherein said heparanase is a mature heparanase.  
     
     
         33 . The method of  claim 31 , wherein said heparanase is a pro-heparanase, cleavable into mature heparanase.  
     
     
         34 . The method of  claim 31 , wherein contacting the IVF embryo with an effective amount of heparanase is in vitro.  
     
     
         35 . The method of  claim 31 , wherein contacting the IVF embryo with an effective amount of heparanase is in utero.  
     
     
         36 . The method of  claim 31 , wherein contacting the receptive uterus with the effective amount of heparanase precedes implanting the IVF embryo in the receptive uterus.  
     
     
         37 . The method of  claim 31 , wherein contacting the receptive uterus with the effective amount of heparanase is concurrent to implanting the IVF embryo in the receptive uterus.  
     
     
         38 . An embryo coated with exogenous purified heparanase, said heparanase having or being activatable to have catalytic activity as an active form of a heparanase protein as set forth by SEQ ID NO:5.  
     
     
         39 . The embryo of  claim 38 , wherein said heparanase is a mature heparanase.  
     
     
         40 . The embryo of  claim 38 , wherein said heparanase is a pro-heparanase, cleavable into mature-heparanase.  
     
     
         41 . The embryo of  claim 38 , between 2 cells and a blastocyst.  
     
     
         42 . A pharmaceutical composition comprising, as an active ingredient, an effective amount of isolated and purified heparanase, said heparanase having or being activatable to have catalytic activity as an active form of a heparanase protein as set forth by SEQ ID NO:5, the pharmaceutical composition designed for intra-uterine application.  
     
     
         43 . The pharmaceutical composition of  claim 42 , wherein said heparanase is a mature heparanase.  
     
     
         44 . The pharmaceutical composition of  claim 42 , wherein said heparanase is a pro-heparanase, cleavable into mature heparanase.  
     
     
         45 . A pharmaceutical composition comprising, as an active ingredient, an effective amount of purified heparanase, said heparanase having or being activatable to have catalytic activity as an active form of a heparanase protein as set forth by SEQ ID NO:5, the pharmaceutical composition is designed for application to an embryo in vitro.  
     
     
         46 . The pharmaceutical composition of  claim 45 , wherein said heparanase is a mature heparanase.  
     
     
         47 . The pharmaceutical composition of  claim 45 , wherein said heparanase is a pro-heparanase, cleavable into mature heparanase.  
     
     
         48 . An embryo growth composition comprising an effective amount of nutrients for embryonic growth and an effective amount of purified heparanase for assisting in embryo implantation, said heparanase having or being activatable to have catalytic activity as an active form of a heparanase protein as set forth by SEQ ID NO:5.  
     
     
         49 . The embryo growth composition of  claim 48 , wherein said heparanase is a mature heparanase.  
     
     
         50 . The embryo growth composition of  claim 48 , wherein said heparanase is a pro-heparanase, cleavable into mature heparanase.